FDA Report Offers Complicated Picture of Industry Compliance With Postmarket Requirements
The majority of ongoing postmarketing requirements (PMRs) and postmarketing commitments (PMCs) from Fiscal Years 2013 and 2014 were on schedule, but a large number of companies are still struggling to meet some of these regulatory requirements on time, the US Food and Drug Administration (FDA) said in a new report issued Friday.
The slew of data released by FDA offer a murky look at how drugmakers meet such postmarket requirements once a new drug or biologic is approved, particularly as the number of unique new drug application (NDA) and biologic license application (BLA) applicants with “open” (meaning those that are pending, ongoing, delayed, submitted or terminated) PMRs and/or PMCs remained constant from FY 2013 (256 unique applicants) to FY 2014 (257 unique applicants).
However, some of the data points raise questions about whether companies are dragging their feet on the statutory requirements.
For instance, as of 30 September 2014, only 45% (57/128) of the PMRs established in FY 2008 were fulfilled (though 22% (28/128) were released, meaning FDA said they were unnecessary or no longer feasible).
And for NDAs and BLAs that won accelerated approval in FYs 2013 and 2014, only three PMRs have been submitted to FDA while 79 are either pending or ongoing.
Background
A PMR is a study or clinical trial that an applicant is required by statute or regulation to conduct following the approval of a drug or biologic. A PMC, meanwhile, is a study or clinical trial that an applicant agrees in writing to conduct following approval, but that is not required by statute or regulation.
Under the regulations, applicants are required to submit annually a report on the status of each clinical safety, clinical efficacy, clinical pharmacology and nonclinical toxicology study or clinical trial, either required by FDA or that they have committed to conduct, either at the time of approval or after approval.
An applicant must report on the progress of the PMR/PMC within 60 days of the anniversary of the drug product’s approval until the PMR/PMC is completed or terminated and FDA determines that the PMR/PMC has been fulfilled or that the PMR/PMC is either no longer feasible or would no longer provide useful information.
For its own reporting purposes, FDA has established terms to describe when the conditions of the PMR/PMC have and have not been met, and when the agency has determined that a PMR/PMC is no longer necessary. Such terms include:
- Pending: The study or clinical trial has not been initiated (i.e., no subjects have been enrolled or animals dosed), but does not meet the criteria for delayed (i.e., the original projected date for initiation of subject accrual or initiation of animal dosing has not passed).
- Ongoing: The study or clinical trial is proceeding according to or ahead of the original schedule.
- Delayed: The study or clinical trial is behind the original schedule.
- Terminated: The study or trial was ended before completion, but a final report has not been submitted to FDA.
- Submitted: The study or trial has been completed or terminated, and a final report has been submitted to FDA.
- Fulfilled: The final report for the study or clinical trial was submitted to FDA and FDA notified the applicant that the requirement or commitment was fulfilled through written correspondence.
- Released: FDA has informed the applicant in writing that it is released from its obligation to conduct the study or clinical trial because the study or clinical trial is no longer feasible, would no longer provide useful information or the underlying application has been formally withdrawn.
But even FDA cautions that the data can be difficult to decipher across years and the agency stops short of offering any definitive conclusions in the report.
“It is important to note that a comparison of the number of open and on-schedule or off-schedule PMRs/PMCs over time can be misleading because it does not take into account that the cohort of open PMRs/PMCs is not static from year to year,” FDA says. “New PMRs/PMCs are continually being established for studies and clinical trials with varying start dates and durations; and other PMRs/PMCs are closed because they are either fulfilled or released.”
FDA’s Findings
For applicants submitting status updates on the progress of each open PMR/PMC within 60 days of the anniversary date of approval, the agency found that in 2013, 60% of NDAs and 69% of BLAs were received on time, while 21% of NDAs and 20% of BLAs were not received on time, and 19% of NDAs and 11% of BLAs were not received at all.
Similarly, in FY 2014, of the annual reports due, 58% (265/454) of NDAs and 63% (73/115) of BLAs were received on time, while 19% (88/454) of NDAs and 19% (20/115) of BLAs were not received on time. And almost a quarter of such reports (22% (101/454) for NDAs) were not received during the year, while 19% (22/115) of BLAs were not received during FY2014.
However, FDA makes clear that as of 30 September 2013, most open PMRs (84% for NDAs and 89% for BLAs) and most open PMCs (77% for NDAs and 74% for BLAs) were progressing on schedule (i.e., were not delayed or terminated).
Similarly, as of 30 September 2014, most open PMRs (87% for NDAs and 88% for BLAs) and most open PMCs (68% for NDAs and 77% for BLAs) were also progressing on schedule.
As for those that were not progressing as planned, FDA found that as of 30 September 2014, 13% (126/943) of the open NDA PMRs were off-schedule, and of those, 94% (118/126) were off-schedule because they were delayed while the remaining (8/126) were terminated.
Similarly, at the end of FY2014, 12% (24/194) of the open BLA PMRs were off-schedule and the vast majority (88%; 21/24) were off-schedule because they were delayed.
Editor's note: This article was updated on 10/31 with a link to the report in the first paragraph.